Histologic Features Associated with Kidney Survival in Scleroderma Renal Crisis

Area of Science:

• Nephrology
• Rheumatology
• Pathology

Background:

• Scleroderma renal crisis (SRC) is a severe systemic sclerosis complication with high morbidity and mortality.
• Limited data exist on factors influencing renal outcomes in SRC.
• This study aimed to describe renal histopathology in SRC and its association with kidney failure.

Purpose of the Study:

• To characterize renal histopathology in scleroderma renal crisis.
• To identify histological patterns associated with kidney failure in SRC patients.
• To investigate complement system activation in kidney biopsies from SRC patients.

Main Methods:

• Retrospective French multicenter study of 65 patients with SRC undergoing kidney biopsy (2006-2020).
• Non-supervised hierarchical cluster analysis to identify histological patterns.
• Cox model for kidney failure risk; multiplex immunofluorescence and proximity ligation assay for complement activation.

Main Results:

• Identified 3 distinct histological patterns of kidney injury in SRC.
• Acute arteriolar thrombotic microangiopathy and onion skinning independently predicted kidney failure.
• Complement classical pathway activation (C3 convertase) and terminal pathway deposition (C5b-9) were observed in injured vessels.

Conclusions:

• Scleroderma renal crisis exhibits heterogeneous kidney injury patterns.
• Acute arteriolar thrombotic microangiopathy and onion skinning are key predictors of kidney failure in SRC.
• Complement system activation plays a role in the pathogenesis of kidney injury in SRC.